A revised modular approach to (–)-trans-Δ 8 -THC and derivatives through late-stage Suzuki–Miyaura cross-coupling reactions

A revised modular approach to various synthetic (–)-trans-Δ 8 -THC derivatives through late-stage Suzuki–Miyaura cross-coupling reactions is disclosed. Ten derivatives were synthesized allowing both sp 2 - and sp 3 -hybridized cross-coupling partners with minimal β-hydride elimination. Importantly, we demonstrate that a para-bromo-substituted THC scaffold for Suzuki–Miyaura cross-coupling reactions has been initially reported incorrectly in recent literature

A Revised Modular Approach to D8-THC and Derivatives Through Late-Stage Suzuki-Miyaura Cross-Coupling Reactions

In this manuscript we describe a modular pathway to synthesize biologically relevant (–)-trans-Δ8-THC derivatives, which can be used to modulate the pharmacologically important CB1 and CB2 receptors. This pathway involves a one-pot Friedel-Crafts alkylation/cyclization protocol, followed by Suzuki-Miyaura cross-coupling reactions and gives rise to a series of new Δ8-THC derivatives. In addition, we demonstrate using extensive NMR evidence that similar halide-substituted Friedel-Crafts alkylation/cyclization products in previous articles were wrongly assigned as the para-isomers, which also has consequence for the assignment of the subsequent cross-coupled products and interpretation of their biological activity. Considering the importance of the availability of THC derivatives in medicinal chemistry research and the fact that previously synthesized compounds were wrongly assigned, we feel this research is describing a straightforward pathway into new cannabinoids.</p

A revised modular approach to (–)-trans-Δ \u3csup\u3e8\u3c/sup\u3e -THC and derivatives through late-stage Suzuki–Miyaura cross-coupling reactions

\u3cp\u3e A revised modular approach to various synthetic (–)-trans-Δ \u3csup\u3e8\u3c/sup\u3e -THC derivatives through late-stage Suzuki–Miyaura cross-coupling reactions is disclosed. Ten derivatives were synthesized allowing both sp \u3csup\u3e2\u3c/sup\u3e - and sp \u3csup\u3e3\u3c/sup\u3e -hybridized cross-coupling partners with minimal β-hydride elimination. Importantly, we demonstrate that a para-bromo-substituted THC scaffold for Suzuki–Miyaura cross-coupling reactions has been initially reported incorrectly in recent literature. \u3c/p\u3

Data underlying the article: A Revised Modular Approach to (–)-trans-Δ8-THC and Derivatives Through Late-Stage Suzuki–Miyaura Cross-Coupling Reactions

A revised modular approach to various synthetic (–)-trans-Δ8-THC derivatives through late-stage Suzuki–Miyaura cross-coupling reactions is disclosed. Ten derivatives were synthesized allowing both sp2- and sp3-hybridized cross-couplingpartners with minimal β-hydride elimination. Importantly, we demonstrate that a para-bromo-substituted THC scaffold for Suzuki–Miyaura cross-coupling reactions has been initially reported incorrectly in recent literature

Readily Accessible Strained Difunctionalized trans-Cyclooctenes with Fast Click and Release Capabilities

The click reaction between a functionalized trans-cyclooctene (TCO) and a tetrazine is a compelling method for bioorthogonal conjugation in combination with payload releasing capabilities. However, the synthesis of difunctionalized TCOs remains challenging. As a result, these compounds are poorly accessible, which impedes the development of novel applications. In this work, the scalable and accessible synthesis of a new bioorthogonal difunctionalized TCO is reported in only four single selective steps starting from commercially available compounds. The click kinetics and payload release were assessed with various functionalized derivatives and local drug release was shown in a cellular toxicity study

Data underlying the article: A Revised Modular Approach to (–)-trans-Δ8-THC and Derivatives Through Late-Stage Suzuki–Miyaura Cross-Coupling Reactions

A revised modular approach to various synthetic (–)-trans-Δ8-THC derivatives through late-stage Suzuki–Miyaura cross-coupling reactions is disclosed. Ten derivatives were synthesized allowing both sp2- and sp3-hybridized cross-couplingpartners with minimal β-hydride elimination. Importantly, we demonstrate that a para-bromo-substituted THC scaffold for Suzuki–Miyaura cross-coupling reactions has been initially reported incorrectly in recent literature

Luminescent Assay for the Screening of SARS-CoV-2 MPro Inhibitors

Since the outbreak of SARS-CoV-2 in December 2019 millions of infections have been reported globally. The viral chymotrypsin-like main protease (MPro) exhibits a crucial role in viral replication and represents a relevant target for antiviral drug development. In order to screen potential MPro inhibitors we developed a luminescent assay using a peptide based probe containing a cleavage site specific for MPro. This assay was validated showing IC50 values similar to those reported in the literature for known MPro inhibitors and can be used to screen new inhibitors